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ACTEMRA/RoACTEMRA inhibits the actions

of IL-6, the most abundant cytokine in

the rheumatoid synovium and a key

driver of chronic inflammation

and autoimmunity1

Mechanism of Action

A First-in-class IL-6 Receptor Inhibitor

  • ACTEMRA/RoACTEMRA (tocilizumab) is the only approved biologic therapy that targets the interleukin-6 (IL-6) receptor.2-5
    • IL-6 has a pivotal role in cell signalling and is associated with diverse physiological effects that contribute to the system-wide pathogenesis of RA (summarised in the short animated video below).6,7
    • In addition to its key role in joint inflammation and destruction,7 IL-6 also induces hepatic production of acute-phase proteins, such as hepcidin and
      C-reactive protein (CRP).8,9
    • By reducing iron absorption and combined with the sequestration of iron in macrophages, elevated hepcidin levels can decrease haemoglobin levels.8 IL-6 can also contribute towards the marked fatigue experienced by patients.10
    • CRP is a marker of systemic inflammation and increased levels have been correlated with worsening RA symptoms.9 In addition elevated levels of CRP are associated with increased risk of cardiovascular disease, the primary cause of mortality in RA patients.11,12
  • ACTEMRA/RoACTEMRA binds both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), thereby preventing the signalling associated with IL-6 binding to its receptor.13
    • In clinical studies, consistent with the effect of IL-6 on acute-phase reactants, treatment with ACTEMRA/RoACTEMRA was associated with rapid decreases in CRP and increases in haemoglobin levels.13

ACTEMRA/RoACTEMRA inhibits IL-6-mediated signalling

ACTEMRA/RoACTEMRA: A biologic for the treatment of RA

  • ACTEMRA/RoACTEMRA is a novel IgG1 monoclonal antibody against the human
    IL-6 receptor.4,5,13 Although based on a mouse monoclonal antibody ACTEMRA/RoACTEMRA is produced using recombinant DNA engineering to generate an antibody partially (90–95%) derived from human DNA, a process known as humanising. Humanised antibodies generally have a lower antigenic potential than mouse or chimeric antibodies.

ACTEMRA/RoACTEMRA: a humanised antibody with a low potential for antigenicity

References:
1. Choy E, et al. N Engl J Med 2001; 344:907-916. 2. Hirata Y, et al. J Immunol 1989; 143:2900–2906. 3. Takagi N, et al. Arthritis Rheum 1998; 41:2117–2121. 4. Mihara M, et al. Clin Immunol 2001; 98:319–326. 5. Yoshizaki K, et al. Springer Semin Immunopathol 1998; 20:247–259. 6. Choy E. Ann Rheum Dis 2003; 62 (Suppl 2):ii68–ii69. 7. Choy E. Rheum Dis Clin North Am 2004; 30:405–15, viii. 8. Nemeth E, et al. J Clin Invest 2004; 113:1271-1276. 9. Gabay C and Kushner K. N Engl J Med 1999; 340:448–454. 10. Nishimoto N. Curr Opin Rheumatol 2006; 18:277-281. 11. del Rincón I, et al. Arthritis Rheum 2001;44:2737–2745. 12. Turesson C, et al. Ann Rheum Dis 2004;63:952–955. 13. RoACTEMRA® (tocilizumab) Summary of Product Characteristics. Roche Registration Limited. August 2011. 14. Heinrich PC, et al. Biochem J 1998; 334 (Pt 2):297–314. 15. Heinrich PC, et al. Biochem J 2003; 374:1–20.

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